CN110177822A - The synthesis of polycarbonate siloxane glycol - Google Patents

The synthesis of polycarbonate siloxane glycol Download PDF

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CN110177822A
CN110177822A CN201680042097.XA CN201680042097A CN110177822A CN 110177822 A CN110177822 A CN 110177822A CN 201680042097 A CN201680042097 A CN 201680042097A CN 110177822 A CN110177822 A CN 110177822A
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polycarbonate
product
group
reaction mixture
medical apparatus
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CN110177822B (en
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F·P·马奎尔
S·文卡塔拉玛尼
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Autec Biomaterials Co Ltd
International Open Ltd
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International Open Ltd
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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/61—Polysiloxanes
    • C08G18/615—Polysiloxanes containing carboxylic acid groups
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/26—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/04—Macromolecular materials
    • A61L29/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G64/00—Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
    • C08G64/02—Aliphatic polycarbonates
    • C08G64/0208—Aliphatic polycarbonates saturated
    • C08G64/0225—Aliphatic polycarbonates saturated containing atoms other than carbon, hydrogen or oxygen
    • C08G64/0266—Aliphatic polycarbonates saturated containing atoms other than carbon, hydrogen or oxygen containing silicon
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G64/00—Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
    • C08G64/18—Block or graft polymers
    • C08G64/186—Block or graft polymers containing polysiloxane sequences
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G64/00—Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
    • C08G64/20—General preparatory processes
    • C08G64/30—General preparatory processes using carbonates
    • C08G64/305—General preparatory processes using carbonates and alcohols
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
    • C08G77/42—Block-or graft-polymers containing polysiloxane sequences
    • C08G77/445—Block-or graft-polymers containing polysiloxane sequences containing polyester sequences
    • C08G77/448—Block-or graft-polymers containing polysiloxane sequences containing polyester sequences containing polycarbonate sequences

Abstract

The present invention provides polycarbonate, preparation method and its purposes in the block copolymer such as polyurethane synthesis that copolymer is especially used for biomedical applications based on silicon.

Description

The synthesis of polycarbonate siloxane glycol
Priority claim
This application claims the equity for the U.S. Provisional Patent Application Serial No. 62/172,657 that on June 8th, 2015 submits, Full content is incorporated herein by reference.
Background of invention
The block copolymer usually microphase-separated caused by the unmixability as segment obtains good engineering properties.Example Such as, it is known that in thermoplastic polyurethane elastomer, so-called " hard " segment and " soft " segment have limited miscible and Separation is to form micro- domain.Many performances of polyurethane elastomer can with hypocrystalline hard domains soft Medium Culture provide enhancement effect or Filler shape effect carrys out reasonable dismissal.Soft matrix or domain most often include poly- (alkylidene of the molecular weight in about 500 to 2000 ranges Ether) or polyester chain.This short polymer chain usually with it is hydroxy-end capped and be referred to as " macromolecular diol (macrodiol) ".
The structure of macromolecular diol plays an important role in the aspect of performance for determining block copolymer.Big point based on polyester Sub- glycol usually has good engineering properties, but resistance in the adverse circumstances encountered in such as ocean and biomedical applications Degradability is poor.
Polyethers macromolecular diol provides the stability of enhancing, but is not suitable for synthesizing dead-soft material, ought especially need height When stability.
Polymer based on polysiloxanes, especially dimethyl silicone polymer (PDMS) show such as reduced TG and turn Temperature；The characteristic of good thermal stability, oxidation stability and hydrolytic stability and low-surface-energy.These performances are in block It is ideal in the component derived from macromolecular diol of copolymer.In addition, they show it is good with biological tissue and liquid Good compatibility and toxicity is low.For these reasons, PDMS is found in the building of medical apparatus, particularly implantable device Special application.However, derived from PDMS polymer do not show usually good tensile property such as bending strength or Wearability.
Having paid sizable effort, that low molecular weight PDMS segment is integrated to block copolymer is such as poly- to find Method in urethane.These effort, which focus primarily upon, realizes the well balanced of transparency, machinability and various engineering properties. However, not yet disclosing completely successful trial.
Since there are larger differences in terms of solubility parameter for PDMS and most conventional hard segment, so based on PDMS's Polyurethane is likely to it is characterized in that the material that the height of poor mechanical properties mutually separates.Due between hard segment and soft chain segment in pole Property in terms of this big difference, it is contemplated that premature phase occurs during synthesis and separates and exist composition inhomogeneities and whole low Molecular weight.In addition, the interface between soft domains and hard domains seems that, there are optimal mixability, clearly interface causes for pole Mechanical coupling degree between the two domains is low and leads to intensity difference.It is therefore to be understood that for example, the polyurethane based on PDMS is usual Show the engineering properties gone on business.In general, tensile strength and elongation at break are respectively about 7MPa and 200%.
Polycarbonate macromolecular diol also already functions as synthetic segmented copolymer (blockcopolymer) and block copolymerization The reacted constituent of object (segmented copolymer) system, particularly high performance polyurethane.JP 62,241,920(Toa Gosei Chemical Industry Co.Ltd.)、JP 64,01,726(Dainippon Ink and Chemicals, Inc.)、JP 62,187,725(Daicel Chemical Industries,Ltd.)、DE 3,717,060(Bayer A.G.), U.S. Patent number 4,105,641 (Bayer Aktiengesellschaft), U.S. Patent number 4,131,731 It is disclosed in (Beatrice Foods Company) and U.S. Patent number 5,171,830 (Arco ChemicalTechnology) A series of method for preparing polycarbonate macromolecular diol based on double hydroxy alkylidene compounds.In these patent specifications The most common aklylene glycol of description is 1,6-HD.
Although polycarbonate macromolecular diol is usually categorized under polyester, corresponding polyurethane surface reveals poly- with polyethers Urethane quite or is in some cases better than the hydrolytic stability of polyether-polyurethane.They also have high tensile and tough Property.These performances be attributed to it is high-caliber mix, by being related to the carbonate functional of hard segment carbamate hydrogen and soft chain segment The intermolecular hydrogen bonding of group promotes.The poor elastomer performance that the hydrogen bond is also based on the polyurethane of polycarbonate macromolecular diol is all Such as the reason in part for low malleability and high rigidity meter hardness (durometer hardness).These performances with it is big based on nonpolarity Those of polyurethane of molecule glycol (such as based on those of siloxanes) is opposite.
Therefore it needs to be developed as the block copolymer with the structure feature for showing excellent compatibility and engineering properties The macromolecular diol based on silicon of the structural unit of such as polyurethane.Suitable macromolecular diol will retain the polymer based on silicon The advantages of, such as flexibility, cryogenic property, stability and biocompatibility in some cases.Avoid poor mechanical properties The shortcomings that, allow the macromolecular diol based on silicon to form the application that can be used for various requirement harshness, it is especially biomedical A part of the material in field.
Summary of the invention
Polycarbonate siloxane macromolecular diol is usually with the preparation of single phase ester exchange reaction.New two stages of the invention Method allows the raw material using wider range and reduces the level of by-product.This prepares Polycarbonate-siloxane macromolecular diol Method pass through two-phase method carry out.Such compound is the theme of U.S. Patent number 7,026,423, is incorporated by reference In herein.
The contracting of first stage expression diethyl carbonate (DEC) and bis- (hydroxybutyl) tetramethyl disiloxane (BHTD) parts Poly- reaction.Second stage polymerization includes necessarily being stepped up temperature and reducing reaction pressure (from about 600 supports to about 1 support) to remove Polycondensation by-product is removed, and then increases the molecular weight of polyol product.
Detailed description of the invention
According to an aspect of the invention, there is provided the polycarbonate based on silicon of formula (I):
Wherein,
R1、R2、R3And R4It is identical or different, the straight chain, branch or the cricoid saturation that can be hydrogen or optionally replace or insatiable hunger The alkyl of sum；
R5、R6、R8And R9It is identical or different, it can be the straight chain optionally replaced, branch or cricoid saturated or unsaturated Alkyl；
R7It is divalent linking group or the straight chain optionally replaced, branch or cricoid saturated or unsaturated alkyl；
A is end-capping group；
N, y and z is 0 or bigger integer；With
X is 0 or bigger integer.
Substituent R1、R2、R3And R4Alkyl may include alkyl, alkenyl, alkynyl, aryl or heterocycle.It should be appreciated that Group of equal value may be substituted for base R5、R6、R7、R8And R9, the difference is that, refer to that alkyl, alkenyl and alkynyl should divide It is not alkylidene, alkenylene and alkynylene.In order to avoid repeating, the specific definition of alkyl, alkenyl and alkynyl is hereafter only provided.
Term " alkyl " indicates straight chain, branch or monocycle or multi-ring alkyl, preferably C1-12Alkyl or cycloalkyl.Straight chain and branch The example of alkyl group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl group, sec-butyl, amyl, isopentyl, sec-amyl, 1,2- dimethyl propyl, 1,1- dimethyl propyl, amyl, hexyl, 4- methyl amyl, 1- methyl amyl, 2- methyl amyl, 3- first Base amyl, 1,1- dimethylbutyl, 2,2- dimethylbutyl, 3,3- dimethylbutyl, 1,2- dimethylbutyl, 1,3- dimethyl Butyl, 1,2,2- thmethylpropyl, 1,1,2- thmethylpropyl, heptyl, 5- methylhexyl, 1- methylhexyl, 2,2- dimethyl Amyl, 3,3- dimethyl amyl group, 4,4- dimethyl amyl group, 1,2- dimethyl amyl group, 1,3- dimethyl amyl group, 1,4- dimethyl-penten Base, 1,2,3- trimethyl butyl, 1,1,2- trimethyl butyl, 1,1,3- trimethyl butyl, octyl, 6- methylheptyl, 1- methyl Heptyl, 1,1,3,3- tetramethyl butyl, nonyl, 1-, 2-, 3-, 4-, 5-, 6- or 7- Methyl Octyl, 1-, 2-, 3-, 4- or 5- second Base heptyl, 1-, 2- or 3- propyl hexyl, decyl, 1-, 2-, 3-, 4-, 5-, 6-, 7- and 8- Nonyl, 1-, 2-, 3-, 4-, 5- Or 6- ethyloctanyl, 1-, 2-, 3- or 4- propylheptyl, undecyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- the or 9- methyl last of the ten Heavenly stems Base, 1-, 2-, 3-, 4-, 5-, 6- or 7- ethylnonanyl, 1-, 2-, 3-, 4- or 5- propyl octyl, 1-, 2- or 3- butyl heptyl, 1- Amyl hexyl, dodecyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9- or 10- methylundecyl, 1-, 2-, 3-, 4-, 5-, 6-, 7- or 8- ethyl decyl, 1-, 2-, 3-, 4-, 5- or 6- propyl nonyl, 1-, 2-, 3- or 4- butyl octyl, 1,2- amyl heptan Base etc..The example of naphthenic base includes cyclopropyl, cyclobutyl, cyclopenta, cyclohexyl, suberyl, cyclooctyl, cyclononyl and cyclodecyl Deng.
The group that term " alkenyl " expression is formed by straight chain, branch or monocycle or polycyclic olefin, including olefinic are single or multiple not The alkyl or cycloalkyl as defined above of saturation, preferably C2-12Alkenyl.The example of alkenyl includes vinyl, allyl, 1- methyl Vinyl, cyclobutenyl, isobutenyl, 3- methyl-2-butene base, 1- pentenyl, cyclopentenyl, 1- methyl cyclopentene base, 1- oneself Alkenyl, 3- hexenyl, cyclohexenyl group, 1- heptenyl, 3- heptenyl, 1- octenyl, cyclo-octene base, 1- nonenyl, 2- nonenyl, 3- nonenyl, 1- decene base, 3- decene base, 1,3- butadienyl, 1,4- pentadienyl, 1,3- cyclopentadienyl group, 1,3- oneself two Alkenyl, 1,4- hexadienyl, 1,3- cyclohexadienyl, 1,4- cyclohexadienyl, 1,3- cycloheptadiene base, 1,3,5- cycloheptatriene Base, 1,3,5,7- cyclooctatetraenyl etc..
Term " alkynyl " indicates the group formed by straight chain, branch or monocycle or polycyclic alkynes.The example of alkynyl includes second Alkynyl, 1- propinyl, 1- and 2- butynyl, 2- methyl -2-propynyl, valerylene base, 3- pentynyl, 4- pentynyl, 2- hexin Base, 3- hexin base, 4- hexin base, 5- hexin base, 10- undecyne base, 4- ethyl -1- octyne -3- base, 7- dodecyne base, 9- ten Diynyl, 10- dodecyne base, 3- methyl-1-dodecyne-3- base, 2- tridecyne base, 11- tridecyne base, 14 alkynyl of 3-, 7- Hexadecine base, 3- octadecyne base etc..
Term " aryl " indicates the aromatic hydrocarbon radical that single multicore is conjugated and condenses.The example of aryl include phenyl, xenyl, Terphenyl, tetrad phenyl, Phenoxyphenyl, naphthalene, tetralyl, anthryl, dihydro anthryl, benzo anthryl, dibenzo anthryl, Phenanthryl etc..
Term " heterocycle " indicates heteroatomic monocycle or multiring heterocyclic that nitrogen, sulphur and oxygen are selected from comprising at least one. Suitable heterocycle includes heterocycle containing N, such as unsaturated 3-6 member heteromonocyclic group group comprising 1-4 nitrogen-atoms, such as pyrroles Base, pyrrolinyl, imidazole radicals, pyrazolyl, pyridyl group, pyrimidine radicals, pyrazinyl, pyridazinyl, triazolyl or tetrazole radical；Include 1-4 The saturation 3-6 member heteromonocyclic group group of a nitrogen-atoms, such as pyrrolidinyl, imidazolidinyl, piperidino or piperazinyl；Include 1-5 It is the unsaturated fused heterocycle moities of a nitrogen-atoms, such as indyl, isoindolyl, indolizine base, benzimidazolyl, quinolyl, different Quinolyl, indazolyl, benzotriazole base or tetrazolo pyridazinyl；Unsaturated 3-6 member heteromonocyclic group group comprising oxygen atom, such as Pyranose or furyl；Unsaturated 3-6 member heteromonocyclic group group comprising 1-2 sulphur atom, such as thienyl；Include 1-2 oxygen The unsaturated 3-6 member heteromonocyclic group group of atom and 1-3 nitrogen-atoms, such as oxazolyl, isoxazolyl (isoazolyl) or evil two Oxazolyl；Saturation 3-6 member heteromonocyclic group group comprising 1-2 oxygen atom and 1-3 nitrogen-atoms, such as morpholinyl；Include 1-2 oxygen The unsaturated fused heterocycle moities of atom and 1-3 nitrogen-atoms, such as benzoxazolyl or benzoxadiazole base；Include 1-2 The unsaturated 3-6 member heteromonocyclic group group of sulphur atom and 1-3 nitrogen-atoms, such as thiazolyl or thiadiazolyl group (thiadiazolyl)；Saturation 3-6 member heteromonocyclic group group comprising 1-2 sulphur atom and 1-3 nitrogen-atoms, such as thiadiazoles Base；And the unsaturated fused heterocycle moities comprising 1-2 sulphur atom and 1-3 nitrogen-atoms, such as benzothiazolyl or benzo Thiadiazolyl group.
In the present specification, " optionally replace " and refer to that group may or may not be by one or more from the following base Group is further substituted with: oxygen, nitrogen, sulphur, alkyl, alkenyl, alkynyl, aryl, halogen, halogenated alkyl, halogenated alkenyl, halo alkynyl, halogen For aryl, hydroxyl, alkoxy, alkenyloxy group, alkynyloxy group, aryloxy group, carboxyl, benzyloxy, halogenated alkoxy, haloalkenyloxy, halogen For alkynyloxy group, haloaryloxy, nitro, nitro alkyl, nitroalkenyl, nitroalkynyl, nitroaryl, heterocyclic nitro base, nitrine Base, amino, alkyl amino, alkenyl amino, alkynylamino, arylamino, benzylamino, acyl group, alkenylacyl, alkynylacyl, Aryl-acyl, acyl amino, acyloxy, aldehyde radical, alkyl sulphonyl, aryl sulfonyl, alkyl sulfonyl-amino, arylsulfonyl Base amino, alkyl sulphonyl oxygroup, aryl sulfonyl oxygroup, heterocycle, heterocyclic oxy group, heterocyclylamino group, halogenated heterocyclic base, alkane Base sulfonyl (sulphenyl), aryl sulfonyl, alkoxy carbonyl (carboalkoxy), aryloxycarbonyl (carboaryloxy), sulfydryl, alkylthio group, arylthio, acyl sulfenyl etc..
It is preferred that z is the integer of 0 to about 50, x is the integer of 1 to about 50.The desired value of n include 0 to about 20, more preferable 0 to About 10.The preferred value of y is 0 to about 10, more preferable 0 to about 2.
Term " end-capping group " is used herein with its wide in range meaning, and including reactive functional groups or comprising anti- The group of answering property functional group.The suitable example of reactive functional groups be alcohol, carboxylic acid, aldehyde, ketone, ester, carboxylic acid halides, acid anhydrides, amine, imines, Thio (thio), monothioester, sulfonic acid and peroxide.Preferably reactive functional groups are alcohol or amine, more preferably alcohol.
Preferred polycarbonate is formula (I) compound that wherein A is OH, is the polycarbonate macromolecular diol of formula (1a) (polycarbonate siloxane glycol):
Wherein,
R1To R6、R8、R9, n, y, x and z as defined in above formula (I), R7For divalent linking group or optionally replace straight Chain, branch or cricoid saturation or unsaturated alkyl；
For R7Suitable divalent linking group include O, S and NR, wherein R is hydrogen or the straight chain optionally replaced, branch Or cricoid saturated or unsaturated alkyl.
Particularly preferred polycarbonate macromolecular diol is formula (Ia) compound, wherein R1、R2、R3And R4It is methyl, R8It is Ethyl, R9It is hexyl, R5And R6It is propyl or butyl and R7It is O or-CH2-CH2, more preferably work as R7R when for O5And R6For propyl, With work as R7For-CH2-CH2When R5And R6For butyl.The preferred molecular weight range of the polycarbonate macromolecular diol be about 400 to About 5000, more preferably from about 400 to about 2000.
The present invention also provides the method for the polycarbonate macromolecular diol based on silicon for preparing formula as defined above (Ia), It include make carbonate source with:
(i) glycol based on silicon of formula (II),
Wherein,
R1To R7With definition in n such as above formula (Ia)；Or
(ii) glycol for being not based on silicon of the pure and mild formula of two based on silicon (III) of formula (II) defined in above-mentioned (i) is anti- It answers:
HO—R9—OH(III)
Wherein
R9As defined in above formula (Ia).
This method extends to the polycarbonate based on silicon of preparation formula (I), and way is to include by the macromolecular of formula (1a) Hydroxyl in glycol is converted into the additional step of other reactive functional groups.Side known in the art can be used in the step of converting Method realize, such as oxidation to obtain dicarboxylic acids, using Gabriel method be converted into amine or with end-capping reagent such as diisocyanate, The reaction such as dicarboxylic acids, cyclic acid anhydride.
The source of carbonic ester can be the two of carbonate products or when joined generation carbonic ester or carbonate products Kind or more reagent.It should be appreciated that the source of carbonic ester will include R8Substituent group.Suitable carbonate products include ring-type Carbonic ester such as alkylene carbonates, such as ethylene carbonate or propylene carbonate and linear carbonates such as dialkyl carbonate Base ester or diaryl carbonate, such as dimethyl carbonate, diethyl carbonate or diphenyl carbonate.Preferably, the source of carbonic ester With low molecular weight, the reason is that being easy to remove condensation by-product from reaction mixture.
The glycol based on silicon of formula (II) can be used as commercial product acquisition.For example, can be from ShinEtsu or Silar Laboratories obtains 1,3- bis-hydroxypropyl -1,1,3,3- tetramethyl disiloxane and the bis- hydroxyl butyl -1,1,3,3- four of 1,3- Tetramethyldisiloxane.Hydrosilylation reactions can be used by using disilane compound appropriate and hydroxy-end capped in other It is prepared by olefinic compounds.
It should be appreciated that the glycol of formula (II) can be used alone or as comprising different in two or more structures The mixture of glycol is used to prepare polycarbonate according to the present invention.The presence of silicon or siloxy imparts hydrophobic in glycol Property and flexible nature, this leads to improved elastomer and degradation resistance in the copolymer prepared using these polycarbonate.
In another embodiment, the glycol for being not based on silicon of formula (III) can be with the glycol based on silicon of formula (II) Combination is used to prepare polycarbonate.Preferably, the glycol for being not based on silicon is aliphatic dihydroxy compound, such as alkylidene two Alcohol, such as 1,4-butanediol, 1,6- hexylene glycol, diethylene glycol (DEG), triethylene glycol, Isosorbide-5-Nitrae-cyclohexanediol or 1,4-CHDM.? It has been observed that gained polycarbonate is usually random copolymerization carbonic ester when reacting containing silicon diol and aklylene glycol.Therefore, lead to Cross the polycarbonate for selecting both glycol of different ratios that can prepare the property with wide scope.
The method for being used to prepare polycarbonate is preferably ester similar with method described in United States Patent (USP) 4,131,731 and hands over Reaction is changed, is carried out in the presence of ester exchange catalyst.The example of suitable catalyst is included in U.S. Patent number 5,811,427 Disclosed in those, such as stannous octoate and dibutyl tin dilaurate.
It should be appreciated that other methods can be used to prepare polycarbonate of the invention, such as by Eckert5Et al. description Those of, these documents are incorporated herein by reference.Some in these methods include making carbonate source and formula (II) (for example, Cl-COO-R '-OCOCl, wherein R' is divalent linking group or appoints by glycol and phosgene (ClCOCl) or chloro-formate Choose straight chain, branch or the cricoid saturated or unsaturated alkyl in generation) reaction.
Polycarbonate of the invention can be used for preparing copolymer, and such as copolyesters, copolyamide, is total to copolymerization ether carbonate Polyimides or block copolymer such as polyurethane or polyurethane-urea elastomer.
Therefore, invention further provides the copolymers of the polycarbonate segment based on silicon comprising formula (Ib):
Wherein
R1To R9, definition in n, y, x and z such as above formula (I).
Polycarbonate of the invention is particularly useful in preparing polyurethane elastomeric compositions.
According to another aspect of the invention, a kind of polyurethane elastomeric compositions are provided, it includes formulas defined above (Ib) the polycarbonate segment based on silicon, wherein R7It is divalent linking group or the straight chain optionally replaced, branch or cricoid Saturated or unsaturated alkyl.
Polyurethane elastomeric compositions of the invention can be prepared by any suitable technology.Preferably method includes Polycarbonate and chain extender are mixed, the mixture and di-isocyanate reaction are then made.Initial Composition preferably at about 45 DEG C extremely It about 100 DEG C, mixes at a temperature of more preferably from about 60 DEG C to about 80 DEG C ranges.If desired, being calculated based on whole components, content is The catalyst such as dibutyl tin dilaurate of about 0.001 weight % to about 0.5 weight % can be added in original mixture. Mixing can be in conventional equipment or in the limitation space of reactive extruder or successive reaction injection (mo(u)lding) machine (confines) it is carried out in.
Alternatively, polyurethane can be prepared by prepolymer process, this method includes keeping diisocyanate anti-with polycarbonate It should be to form the prepolymer with terminal-reactive diisocyanate ester group.The prepolymer and then and chain extender reaction.
Therefore, polyurethane elastomeric compositions of the invention can be further defined as the reaction production comprising following substance Object:
(i) polycarbonate based on silicon of formula (I) defined above, wherein R7For divalent linking group or optionally replace Straight chain, branch or cricoid saturation or unsaturated alkyl；
(ii) diisocyanate；With
(iii) chain extender.
Preferably, the diisocyanate is selected from 4,4'- methylenediphenyl diisocyanates (MDI), di-2-ethylhexylphosphine oxide (ring Hexyl) diisocyanate (H12MDI), to phenylene vulcabond (p-PDI), trans-cyclohexane -1,4- diisocyanate (CHDI) or the mixture of its cis and trans isomer, 1,6- hexamethylene diisocyanate (DICH), 2,4- toluene two are different Cyanate (2,4-TDI) or its isomers or mixture, to tetramethylxylene diisocyanate (p-TMXDI) and tetramethyl Xylene diisocyanate (m-TMXDI).MDI is particularly preferred.
The chain extender is preferably selected from 1,4- butanediol, 1,6-HD, 1,8- ethohexadiol, 1,9- nonanediol, the 1,10- last of the ten Heavenly stems Bis- (2- hydroxyl-oxethyl) benzene of glycol, 1,4 cyclohexane dimethanol, paraxylene glycol, 1,4- and 1,12- dodecanediol.1, 4- butanediol is particularly preferred.
A kind of particularly preferred polyurethane elastomeric compositions of the invention include the reaction product of following substance:
(i) compound of formula (Ia), wherein R1、R2、R3And R4It is methyl, R8It is ethyl, R9It is hexyl, R5And R6It is propyl Or butyl, R7It is O or-CH2—CH2—；
(ii)MDI；With
(iii) 1,4- butanediol.
It is poly- that the advantages of introducing polycarbonate segment is relatively easy such as extrusion, injection molding and compression moulding processing by conventional method Urethane processes wax without adding.However, if it is desired to during preparation can be by conventional polyurethanes processing additives such as Catalyst, antioxidant, stabilizer, lubricant, dyestuff, pigment, inorganic and/or organic filler and reinforcing material are integrated to poly- ammonia In ester.Such additive is preferably added in polycarbonate.
The polycarbonate, diisocyanate and chain extender can exist with certain proportion.(i.e. two is different for hard segment in composition Cyanate and chain extender) preferred content be about 30 weight % to about 60 weight %, more preferably 40 weight % to 50 weight %.
Polyurethane elastomeric compositions of the invention are particularly useful for the material that preparation has good mechanical properties, especially Biomaterial.
According to another aspect of the present invention, it provides with improved engineering properties, transparency, machinability and/or resistance to The material of degradability, it includes polyurethane elastomeric compositions, the polyurethane elastomeric compositions include formula defined above (Ib) polycarbonate segment.
The present invention also provides polyurethane elastomeric compositions defined above to be used as with improved engineering properties, transparent The purposes of the material of degree, machinability and/or degradation resistance.
When being used as the material with improved engineering properties, transparency, machinability and/or degradation resistance, the present invention Further provide polyurethane elastomeric compositions defined above.
Improved engineering properties includes tensile strength, tearing strength, wearability, hardometer (Durometer) hardness, scratches The correlation measurements of bent modulus and flexibility or elasticity.
Improved degradation resistance includes the patience to free radical, oxidation, enzymatic and/or hydrolytic process, and to working as conduct Degradation resistance when biomaterial is implanted into.
Improved machinability includes being easy to by being cast such as solvent cast and thermally such as squeezing out and be molded It is low sticky and opposite from gel after processing, such as extrusion.
Additionally provide the degradation resistant material comprising polyurethane elastomeric compositions defined above.
Polyurethane elastomeric compositions of the invention show good elastomer performance.It should also be in biotic environment With good compatibility and stability, especially when implanting for a long time.
According to another aspect of the present invention, a kind of resistance to material degraded in vivo is provided, it includes poly- ammonia defined above Ester elastomer composition.
The polyurethane elastomeric compositions are also used as biomaterial.Term " biomaterial " herein with it most Extensive meaning uses, and refers to and use in the case where it is contacted with living animal or the cell and/or body fluid of the mankind Material.
Therefore, the polyurethane elastomeric compositions can be used for manufacturing medical apparatus, product or implantation material.
Therefore, the present invention also provides the doctors being completely or partially made of polyurethane elastomeric compositions defined above With device, product or implantation material.
The medical apparatus, product or implantation material may include pacemaker and defibrillator, conduit, intubation, implantable vacation Body, heart-assist device, heart valve, blood vessel graft, device outside, man-made organ, pacemaker wires, defibrillator leads, It is blood pump, air pocket pump, A-V current divider, biosensor, the film for cell cladding, drug delivery device, wound dressing, artificial Joint, orthopaedic implants and soft tissue replacement.
It should be appreciated that having the elastic polyurethane optimized for constructing the property of various medical apparatus, product or implantation material Body composition will also have other non-medical applications.Such application may include them in manufacture rtificial leather, sole；Cable Sheath；Varnish and coating；The structure member of pump, vehicle etc.；Mining trommel and conveyer belt；It is laminated blend, such as in glass In glass window；Textile；Seperation film；Sealant or as the purposes in the component of adhesive.
It is also understood that the silicone components of the polyurethane elastomeric compositions will be provided for by its dielectric property The chance of electronics and electric component and insulator.
Therefore, the present invention extends to use of the polyurethane elastomeric compositions defined above in manufacturing device or product On the way.
The present invention also provides the device being completely or partially made of polyurethane elastomeric compositions defined above or Product.
Embodiment
The preparation of 1. polycarbonate siloxane glycol (Ia) of embodiment
A. raw material
By the diethyl carbonate that uses as former state when receiving, (anhydrous 99%), is gone at four titanium butoxides (TBT) (SILVER REAGENT 97%) Ionized water, methylene chloride (chrome AR), sodium sulphate (anhydrous granular 99%), active carbon.Two silicon oxygen of dihydroxy butyl tetramethyl Alkane (BHTD) is using preceding purifying.
B. feed purification
It is purified from one of the received raw material of supplier BHTD.In BHTD synthesis, ethyl iodide and iodine have been used. The iodine for the even trace being present in BHTD can also interfere with synthesis.In order to remove iodine from BHTD, active carbon is used.For more Active carbon facilitates purified feed stock before first alcohol synthesis.For this purpose, the active carbon of 2%w/w is added in BHTD and to stir 24 small When.Then resulting active carbon slurries are filtered through 50 μ Eaton filter bags and 0.45 μ cartridge filter under a nitrogen.It obtains It uses 2% active carbon to handle again by the BHTD that an active carbon is handled and stirs 24 hours, then pass through 0.45 μ filter mistake Filter.The loss of each active carbon processing is about 10%.
C. first stage (1 kilogram of batch of material):
BHTD (813.66g, 1M) and four titanium butoxides (TBT) (4.07g, 0.5% BHTD) are placed in and are stirred equipped with machinery It mixes in the 2L three neck round bottom of device, still and Liebig condenser.Oil bath temperature is risen to 130 DEG C, it is small through 1 with peristaltic pump When be added diethyl carbonate (186.34,0.54M).Reaction is further continued for carrying out 1 hour at the same temperature under reflux, and with 150rpm stirring.
D. second stage:
After reflux 1 hour, one end of Liebeg condenser is connected on still, the other end connects 1 liter of round-bottomed flask To distill by-product and azeotropic mixture.Then temperature is gradually risen to 150 DEG C, while vacuum is gradually increased into 1 support.With Predetermined time interval changes temperature, vacuum and removes distillate.Final stage after being decanted at second, will entirely react mixed Object is closed to flow back 1 hour under 150 DEG C, 1 support.Then stop reacting and being cooled to room temperature (about 20-30 DEG C), obtaining molecular weight is 520 to 650 coarse polycarbonate siloxane glycol.
E. catalyst inactivation:
In order to make catalyst inactivation, deionized water (batch scale is added into cooling coarse polycarbonate siloxane glycol 20%).Mixture flows back 1 hour at 130 DEG C.With predetermined time interval by the way that vacuum degree is increased to 1 from about 200 supports Support is to be evaporated off water.Final product is cooling and be dissolved in be made in methylene chloride 50% solution.The solution is passed through into sodium sulphate bed Vacuum filter, and active carbon processing (2%w/w of batch sizes) are carried out at room temperature overnight.After 24 hours, pass through under a nitrogen 50 μ Eaton bag filters and 0.45 ± 0.2 μ Sartorius cartridge filter pressure filtration.
F. it strips:
With 2, " stripper strips the polycarbonate siloxane glycol of filtering in methylene chloride twice.It strips for the first time With 15ml/ minutes removing solvents under 70 DEG C, vacuum.Second stripping at 145 DEG C with 4ml. minute removing trace solvents with The fraction of lower molecular weight.It will tightly seal through steam stripped polycarbonate siloxane dihydric alcohol and store at room temperature.Yield About 65%.Molecular weight is about 600.
The all publications, patents and patent applications referred in this specification are incorporated herein by reference, degree as Each individually publication, patent or patent application, which specifically and individually indicate, to be herein incorporated by reference.Passing through reference In the case that the definition for the term being incorporated to conflicts with term defined herein, then answer subject to the present specification.

Claims (9)

1. a kind of method for being used to prepare polycarbonate siloxane macromolecular diol comprising:
(a) by the carbonate source such as dialkyl carbonate of about 2 equivalents or bis- (hydroxyls of two carbonic ester of alkylidene and about 1 equivalent Alkyl) such as bis- (hydroxybutyl) tetramethyl disiloxanes of tetramethyl disiloxane and initiator catalyst such as four butoxy Titanium about 120-140 DEG C such as about 130 DEG C at a temperature of be mixed to form reaction mixture；
(b) by the reaction mixture be heated to about under stiring 120-140 DEG C such as to about 130 DEG C about 0.5-2.0 hours it is all Such as from about 1 hour；
(c) heated reaction temperature is increased to about 140-175 DEG C, while vacuum is increased into about 1 support；
(d) reaction mixture such as about 1 hour about 0.5-2 hours of heating is flowed through next time in about 1 support；With
(e) heated reaction mixture is cooled to about 20-30 DEG C, to obtain polycarbonate siloxane macromolecular diol and institute State the mixture of catalyst.
2. method of claim 1 further includes making the catalyst inactivation through in cooling reaction mixture.
3. method for claim 2, including adding water to through in cooling reaction mixture, in about 125-140 DEG C, about 200 supports Lower reflux mixture 1 hour, and vacuum is increased into about 1 support to remove water, to obtain polycarbonate siloxane macromolecular two Alcohol.
4. the material with improved engineering properties, transparency, machinability and/or degradation resistance, it includes elastic polyurethanes Body composition, the polyurethane elastomeric compositions include derived from the polycarbonate silicon prepared as defined in claim 3 The polycarbonate segment based on silicon of oxygen alkane macromolecular diol.
5. the medical apparatus, product or the implantation that are entirely or partly made of the urethane composition defined in claim 4 Object.
6. the medical apparatus of claim 5, product or implantation material, wherein the medical apparatus, product or implantation material are that heart rises It fights device, sensor such as glucose sensor, defibrillator, conduit, heart valve, heart-assist device, blood vessel graft or can It is implanted into prosthese.
7. the material with improved engineering properties, transparency, machinability and/or degradation resistance, it includes such as claims 4 Defined in polyurethane elastomeric compositions.
8. the medical apparatus of claim 5, product or implantation material, wherein the medical apparatus, product or implantation material are intubation, body Outer device, pacemaker wires, defibrillator leads, blood pump, air pocket pump, A-V current divider, biosensor, is used for carefully man-made organ Film, drug delivery device, wound dressing, artificial joint, orthopaedic implants or the soft tissue replacement of born of the same parents' cladding.
9. the device or product that are entirely or partly made of the polyurethane elastomeric compositions defined in claim 4.
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